Acute hepatic failure resulting from a variety of causes has been reported to afflict approximately 2,000 pediatric and adult patients per year in the United States (Berk, P. D. and Popper, H., American Journal of Gastroenterology, 69, 349-400(1988)). In spite of the understandings gained by determining the inciting etiology in 60-80% of hepatic failure cases, treatment of this disease still focuses on patient stabilization and expectant management until either the patient's liver recovers or liver transplantation is carried out. It is reported that liver transplantation has increased the survival rate of fulminant hepatic failure patients from less than 20% to greater than 50% (Tygstrup, N. and Ranek, L., Seminar Liver Disease, 6, 129-137(1986)); Schafer, D. F. and Shaw, B. W. Jr., Seminar Liver Disease, 9,189-194(1989); Campbell, D. A. Tr. et al., American Surgeon, 8, 546-549(1991); Isai, H. et al., Transplantation Proceeding, 24, 1475-1476 (1992)).
However, it is difficult to obtain a timely donor liver, and a patient waiting for a donor liver requires an extracorporeal liver support system until a new liver is procured. Such system renders the patient stable and increases the survival rate after the transplantation.
For many years, it has been assumed that the vast majority of toxins which cause hepatic coma are small dialyzable molecules. As a result, most liver support systems and therapeutic regimens used in the past have relied mainly on blood detoxification. However, the pathogenesis of acute hepatic failure is complex and many investigators have suggested that isolated viable hepatocytes be used in the construction of a liver support system not only to provide detoxification but also to restore missing synthetic functions of the liver. In line with this suggestion, a conventional artificial liver has been designed based on the use of a bioreactor containing isolated living hepatocytes packed typically in hollow fiber membranes.
Although isolated hepatocytes used in the conventional bio-reactor exhibit some desirable effects arising from intercellular interactions thereamong, such effectiveness is limited due to the lack of cell to connective interactions which characterize the liver in its in vivo state. Therefore, the conventional artificial liver has been found to be only marginally effective in various clinical studies. Accordingly, an artificial liver device comprising liver slices or tissues has been proposed by some investigators (Nose, Y. et al., ASAIO Trans., 358-362(1963)); Soyer, T. et al., Surg. Forum, 23, 346(1972); Soyer, T. et al., Am. J. Surg., 126, 20-24(1973); Kimura, K. et al., Artif. Organs, 4, 297-301(1980)), but the development of an efficient system based on the use of liver slices or tissues has not been successful, mainly due to difficulties in maintaining liver slices viable and functional in such a system.